Summary: Consuming seven or more units of alcohol per week is associated with increased levels of iron in the brain. High levels of iron in the brain are associated with an increased risk of neurodegenerative disorders and alcohol-related cognitive decline.
Consuming seven or more units of alcohol per week is associated with higher levels of iron in the brain, according to a study of nearly 21,000 people published July 14 in the journal Open Access. MEDICINE PLOS.
Iron accumulation in the brain has been linked to Alzheimer’s and Parkinson’s diseases and is a possible mechanism of alcohol-related cognitive decline.
There is mounting evidence that even moderate consumption of alcohol can negatively affect brain health. Anya Topiwala at the University of Oxford, UK, and colleagues explored the relationships between alcohol consumption and iron levels in the brain.
20,965 participants from the UK Biobank reported their alcohol consumption, and their brains were scanned using magnetic resonance imaging (MRI).
The livers of nearly 7,000 were also imaged using MRI to assess systemic iron levels. All individuals completed a series of simple tests to assess cognitive and motor function.
The average age of the participants was 55 years and 48.6% were female. Although 2.7% classified themselves as non-drinkers, the average intake was about 18 units per week, which translates to about 7 cans of beer or six large glasses of wine.
The team found that alcohol consumption above seven units per week was associated with higher iron markers in the basal ganglia, a group of brain regions associated with motor control, procedural learning, eye movement, cognition, emotion, and more. Iron accumulation in some areas of the brain has been associated with worse cognitive function.
This is the largest study to date on moderate alcohol consumption and iron accumulation. Although drinking was self-reported and could be underestimated, this was considered the only feasible way to establish such a large intake.
A limitation of the work is that MRI-derived measures are indirect representations of iron in the brain, and other brain changes observed with alcohol consumption can be combined with changes in iron levels.
Given the prevalence of moderate drinking, even small associations can have a significant impact on the entire population, and there can be benefits in interventions to reduce consumption in the general population.
Tubiwala adds, “In the largest study to date, we found that drinking more than seven units of alcohol per week was associated with iron accumulation in the brain. High brain iron in turn is associated with poorer cognitive performance. Iron accumulation could be the basis of alcohol-related cognitive decline.”
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“Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: observational and Mendelian randomization analyzes” by Tubiwala A. et al. MEDICINE PLOS
Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: observational and Mendelian randomization analyzes.
Iron deposition in the brain has been linked to several neurodegenerative conditions and has been reported in alcoholism. It is not known whether iron buildup occurs in moderate heavy drinkers or not. Our goals were to investigate the evidence supporting causal relationships between alcohol consumption and brain iron levels and to examine whether high brain iron represents a potential pathway for alcohol-related cognitive deficits.
METHODOLOGY AND RESULTS
Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from a two-sample Mendelian randomization (MR). Alcohol intake was self-reported via a touch screen questionnaire at baseline (2006 to 2010).
Participants with complete data were included. Multi-organ MRI (9.60 ± 1.10 years after baseline) was used to confirm iron content in each brain region (quantitative sensitivity mapping (QSM) and T2*) and liver tissue (T2*), a marker for systemic iron. The main outcomes were susceptibility (χ) and T2*, the measures used as indicators of iron deposition.
Brain regions of interest included the putamen, caudate, hippocampus, thalamus, and substantia nigra. Possible pathways for alcohol-related brain iron accumulation through elevated systemic iron (liver) stores were explored in a causal mediation analysis.
Cognition was assessed at examination and follow-up online (5.82 ± 0.86 years after baseline). Executive function was assessed with a path-making test, smooth intelligence with puzzle tasks, and reaction time with a task based on the “Snap” card game.
The mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and the drinkers never drank 2.7% of the sample. Alcohol consumption was associated with markers of elevated iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09]And the s <0.001), caudates (β = 0.05 [0.04 to 0.07]And the s <0.001), and dark matter (β = 0.03 .) [0.02 to 0.05]And the s <0.001) and lower iron in the thalamus (β = 0.06 [−0.07 to −0.04]And the s <0.001). وجدت التحليلات المستندة إلى Quintile هذه الارتباطات في أولئك الذين يستهلكون> 7 units (56g) of alcohol per week. MR analyzes provided weak evidence that these relationships are causal.
Genetically predicted weekly alcoholic beverages are positively associated with putamen and hippocampal sensitivity; However, these correlations did not survive multiple test corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher susceptibility to putamen has been observed; However, this was not robust to correct for multiple comparisons. Genetically predicted alcohol use disorder has been associated with serum iron saturation and transferrin.
An elevated liver iron level has been observed with >11 units (88 g) of alcohol per week and less than 7 units (56 g) per week. Systemic iron levels are mediated in part by alcohol intake with iron in the brain. Signs of elevated iron in the basal ganglia associated with slower executive function, lower fluid intelligence, and slower reaction times. Major limitations of the study include that T2* can reflect changes in myelin as well as iron, alcohol use has been self-reported, and MR estimates can be affected by genetic polymorphisms.
To our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption of more than 7 units per week is associated with a higher level of iron in the brain. Iron accumulation represents a potential mechanism of alcohol-related cognitive decline.